Depression is the most common disabling psychiatric illness and the source of enormous human suffering. Depressive symptoms can be identified in over half of all patients seen in psychiatric practice and it is well known that only a small proportion of individuals suffering milder forms of depression ever seek medical attention. That depression feature almost inevitable in the wake of adverse life situations is accepted as part of the human condition. Depressive symptoms, however, also occur in association with chronic illnesses, or as sequelae of both acute and chronic illnesses and injuries, and are often observed in individuals who abuse alcohol, other central nervous system depressants, or narcotics. The Department of Psychiatry (WPIC) of the University of Pittsburgh Medicaa School in collaboration with the Departments of Psychology, Biological Sciences, and Pharmacology has established a MHCRC to investigate the etiology, epidemiology, and treatment of affective disorders. The MHCRC is providing the essential structure and fiscal core support in developing an integrated, multidisciplinary program of investigation, research training, and clinical service. The award of an MHCRC has substantially strengthened our clinical teaching and research programs; a number of scientific disciplines which were not represented are now included; the core support systems (clinical core, biostatistical core, administrative core, technical core, informed consent core, educational core, grants support core and core laboratories) essential for facilitating the integration of participating scientists and programs have been established and the productivity of the faculty has been visibly enhanced. Our clinical research program is organized around the following major themes: psychobiologic investigations; psychosocial factors (assessment and treatment); relationship between developmental stages and affective disorders; epidemiological aspects; and technological improvement of assessment and diagnosis. The basic research activities of the MHCRC is discussed around the four themes of cell-to-cell communication; neural plasticity; stress; and preclinical aspects of depression. In addition a series of new investigations will be developed under the aegis of the MHCRC.